Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

Economic evaluation in psychiatric pharmacogenomics: a systematic review.

Nowadays, many relevant drug-gene associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health care. To address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of PGx testing for the prescription of antidepressants and antipsychotics. From a total of 1159 studies initially identified by literature database querying, and after manual assessment and curation of all of them, a mere 18 studies met our inclusion criteria. Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 drug-gene associations and for combinatorial PGx panels, but evidence is limited for many other drug-gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs, as well as the underreporting of study design elements, which can influence though the economic evaluation. Overall, the findings of this article demonstrate that although there is growing evidence on the cost-effectiveness of genome-guided interventions in psychiatric diseases, there is still a need for performing additional research on economic evaluations of PGx implementation with an emphasis on psychiatric disorders.

Worldwide antipsychotic drug search intensities: pharmacoepidemological estimations based on Google Trends data.

Prescription patterns of antipsychotic drugs (APDs) are typically sourced from country-specific data. In this study, a digital pharmacoepidemiological approach was used to investigate APD preferences globally. Publicly available data on worldwide web search intensities in Google for 19 typical and 22 atypical APDs were temporally and spatially normalized and correlated with reported prescription data. The results demonstrated an increasing global preference for atypical over typical APDs since 2007, with quetiapine, olanzapine, risperidone, and aripiprazole showing the largest search intensities in 2020. Cross-sectional analysis of 122 countries in 2020 showed pronounced differences in atypical/typical APD preferences that correlated with gross domestic product per capita. In conclusion, the investigation provides temporal and spatial assessments of global APD preferences and shows a trend towards atypical APDs, although with a relative preference for typical APDs in low-income countries. Similar data-sourcing methodologies allow for prospective studies of other prescription drugs.

Cost-Sharing Increase, Medication Adherence, and Hospitalizations in Schizophrenia Patients: A Natural Experiment.

Increases in medication cost-sharing rates remain a controversial system-wide cost-containment measure for chronic mental health patients. The objective was to investigate the effects of cost-sharing increases on adherence to prescribed antipsychotic medication and psychiatric hospitalizations among patients with schizophrenia. In July 2012, a Spanish National Law raised the cost-sharing rate from 0 to 10% for pensioner outpatient medication while cost-sharing remained at 0% for other socioeconomic groups. To estimate the effects of the reform, we analyzed the prevalent adult schizophrenic population of Valencia, Spain, followed up 1 year before and after the Law took effect. We used a quasi-experimental design with a patient fixed-effects difference-in-differences regression to evaluate the reform effects on antipsychotic medication adherence, prescription, and hospitalization rates. A total of 5,672 included patients were exposed to the reform, whereas 5,545 were not. There were no differences in adherence, prescription, or hospitalization rates between exposed and nonexposed patients prior to its implementation. The odds ratio of exposed patients remaining adherent to issued prescriptions after the reform took effect were 0.70 99% confidence interval (CI 0.66-0.75), in relation to the nonexposed group. Additionally, the reform was associated with a reduction in exposure to antipsychotic medication (odds ratio (OR) 0.85, 99%CI 0.83-0.88) and an increase in hospitalization risk (OR 1.13, 99% CI 1.05-1.23) during the first year after implementation. Policies raising the cost-sharing rate of medication for patients with schizophrenia are simultaneously associated with unintended effects. We report decreases in antipsychotic exposure and increases in hospitalization rates that lasted for 1 year after follow-up.

Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States. METHODS: In this systematic literature review, MEDLINE® was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted. RESULTS: A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level. CONCLUSIONS: Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.

Cost of the Illness of Treatment-Resistant Schizophrenia: A Mirror Image Study Comparing Clozapine With Other Antipsychotics.

PURPOSE/BACKGROUND: This study aimed to evaluate and compare the cost of illness in patients with treatment-resistant schizophrenia (TRS) during 3 months before starting clozapine and for the initial 3 months of treatment with clozapine. METHODS/PROCEDURES: Fifty-two patients with TRS were evaluated for the cost of illness (direct, indirect, and provider cost) by using a structured questionnaire for the period of 3 months before starting clozapine and then at the end of the 3 months of clozapine therapy. FINDINGS/RESULTS: Total treatment cost for the period of 3 months before starting clozapine was Indian rupees (INR) 40,372 (560.72 US dollars), and the total treatment cost for the first 3 months of clozapine therapy was INR 40,553 (563.23 US dollars). At both the assessments, indirect cost formed the main bulk of the total cost, with no significant difference in the indirect cost. The total direct treatment cost reduced from INR 13,931.6 (193.49 US dollars) to INR 8756 (121.61 US dollars), and the difference between the 2 assessments was statistically significant, with an advantage for clozapine. Overall, after starting clozapine, the total direct cost reduced from 34.5% to 21.6%, and the total indirect cost reduced from 54.3% to 40.2%. After starting clozapine, total provider cost increased from 11.2% to 38.2% of the totalcost. IMPLICATIONS/CONCLUSIONS: Treatment with clozapine is not associated with a significant increase in the overall treatment cost, in the short term. However, there is a significant reduction in direct treatment costs.

Tratamento com aripiprazol para Esquizofrenia no contexto do Sistema Único de Saúde em Goiás: análise de impacto orçamentário e revisão de estudos de análise de custo-utilidade / Aripiprazol for Schizophrenia treatment in the Goiás Public Health System perspective: budget impact analysis and review of cost-utility analysis studies

Tecnologia: Aripiprazol, medicamento antipsicótico de segunda geração. Indicação: tratamento da esquizofrenia. Objetivos: Apresentar evidências de análise econômicas em saúde, no cenário do SUS e contextos internacionais, do tratamento com Aripiprazol para esquizofrenia, comparado a outros antipsicóticos de uso oral de primeira e segunda geração utilizados no SUS. Realizar uma análise de impacto orçamentário para o contexto do SUS em Goiás e estimar uma projeção de gastos diretos com aquisição de Aripiprazol pela Secretaria de Saúde de Goiás, em cenário de incorporação do Aripiprazol para tratamento de esquizofrenia, no período de 2021 a 2025. Materiais e Métodos: Levantamentos bibliográficos nas bases de dados PUBMED e Biblioteca Virtual em Saúde, no mês de junho de 2020. Realizada avaliação da qualidade metodológica das revisões sistemáticas e dos estudos econômicos com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), e Quality of Health Economic Studies (QHES) checklist, respectivamente. Foi calculado o impacto orçamentário, seguindo diretrizes do Ministério da Saúde, e projeção de gastos para a Secretaria de Saúde de Goiás. Resultados: Foram selecionadas e incluídas 1 revisão sistemática e 1 estudo econômico brasileiro no estudo de revisão rápida de evidências. Conclusão: No contexto brasileiro, o Aripiprazol é custo-efetivo, quando comparado a Clorpromazina, Haloperidol, Quetiapina e Ziprasidona. Porém, é menos custo-efetivo que Risperidona e Olanzapina. Caso seja padronizado pela Secretaria de Saúde de Goiás, promoverá economia anual para o SUS de R$ 250.042,05 a R$ 407.418,41, em sua máxima difusão. A projeção de gastos diretos é estimada em R$1.582.115,24 a R$27.960.108,08

Technology: Aripiprazole, second generation antipsychotic medication. Indication: treatment of schizophrenia. Objectives: To show evidence of health economic analysis in the scenario of Brazilian Public Health System (BPHS) and international contexts, for schizophrenia treatment with Aripiprazole, compared to other oral antipsychotics used in BPHS. To make a budget impact analysis for the Goias Public Health System perspective and estimate direct expenditures for the acquisition of Aripiprazole by State Department of Health of Goias, in a scenario of technology incorporation of Aripiprazole for the treatment of schizophrenia, in the period from 2021 to 2025. Materials and Methods: Bibliographical searches were done in the PUBMED and Virtual Health Library databases, in 2020 June. An evaluation of the methodological quality of systematic reviews and economic studies was done using the tools AMSTAR (Assessing the Methodological Quality of Systematic Reviews), and QHES (Quality of Health Economic Studies) checklist, respectively. Calculation of budget impact, following guidelines of the Brazilian Health Ministry, and projection of expenditures for the State Department of Health of Goias. Results: 1 systematic review and 1 Brazilian economic study were selected and included in the study of rapid evidence review. Conclusion: In the Brazilian context, Aripiprazole is cost-effective when compared to Chlorpromazine, Haloperidol, Quetiapine and Ziprasidone. However, it is less cost-effective than Risperidone and Olanzapine. If it is standardized by State Department of Health of Goias, it will promote anual savings for BPHS from R$ 250,042.05 to R$ 407,418.41, in its maximum dissemination. The direct expenses are estimated at R$ 1,582,115.24 to R $ 27,960,108.08

Cost-effectiveness of aripiprazole orally disintegrating tablets in the treatment of schizophrenia in China.

BACKGROUND: Orally disintegrating tablet (ODT) formulation of antipsychotics is one of the innovative drug delivery systems developed to improve medication adherence. We aimed to evaluate the cost-effectiveness of aripiprazole ODT vs. aripiprazole standard oral tablet (SOT), as well as olanzapine SOT in China. METHODS: We developed a discrete event simulation model from government payers' perspective. On the entry, 100,000 patients in each group were simulated for relapse, adverse events, changing adherence level, medication discontinuation, switching or quitting in response to three different medication adherence levels. The model projected quality adjusted life years (QALYs) and treatment costs over a 1-year time horizon. Parameter uncertainties were assessed through sensitivity analyses. RESULTS: The QALYs per patient over 1-year treatment with aripiprazole ODT, aripiprazole SOT, or olanzapine SOT, were 0.7282, 0.7112, and 0.7218, respectively. The corresponding costs were $1,423, $2,215, and $1,493. In both comparisons, aripiprazole ODT was dominant. Compared with aripiprazole SOT and olanzapine SOT, the likelihood of aripiprazole ODT being cost-effective was 99.2% and 69.2%, respectively, using 3 times per capita GDP per QALY as willingness-to-pay threshold. CONCLUSIONS: The aripiprazole ODT is associated with more QALYs at lower costs compared with both aripiprazole SOT and olanzapine SOT in treating schizophrenia in China.

Medication Use and Health Care Utilization After a Cost-sharing Increase in Schizophrenia: A Nationwide Analysis.

BACKGROUND: Increases in prescription drug cost-sharing may decrease adherence to treatment among persons with schizophrenia and lead to discontinuation of use and an increased risk of hospitalization. OBJECTIVE: The objective of this study was to investigate the impact of new deductible and increased drug copayments implemented on antipsychotic and other drug purchases and on rates of hospitalizations and primary care contacts among persons with schizophrenia in Finland. RESEARCH DESIGN: Interrupted time series analysis. SUBJECTS: All persons with schizophrenia in Finland who were alive at the beginning of 2015 (N=41,017). MEASURES: We measured the rates of antipsychotic, other psychotropic and cardiometabolic drug purchasers, hospitalizations, and primary care contacts during 2015 and 2016 with data collected from several nationwide health care registers. RESULTS: During 2016, the proportion of antipsychotic purchasers decreased by -0.26 percentage points per month [95% confidence interval (CI): -0.47 to -0.05] compared with 2015. The trend of other psychotropic purchasers decreased to -0.13 percentage points per month in 2016 (95% CI: -0.22 to -0.04) compared with 2015 and cardiometabolic drug purchases to -0.17 percentage points per month (95% CI: -0.29 to -0.05) compared with 2015. The decreasing trend of psychiatric hospitalizations in 2015 halted in 2016. There were no other significant differences in health care utilization. CONCLUSIONS: In our nationwide time-series analysis, we observed decreases in the slopes of antipsychotic and other drug purchases of persons with schizophrenia after prescription drug cost-sharing increase implementation on January 1, 2016. Policymakers need to be aware of the unintended consequences of increasing cost-sharing among people with severe mental disorders.

Cost of Relapse Management in Patients with Schizophrenia in Italy and Spain: Comparison Between Lurasidone and Quetiapine XR.

BACKGROUND AND OBJECTIVE: Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medical costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective. METHODS: A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A deterministic sensitivity analysis was implemented to test the robustness of the results. RESULTS: The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of - 163.7 € (- 9.0%) and - 327.2 € (- 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of - 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%. CONCLUSIONS: The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetiapine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view.

Systematic review of the methods of health economic models assessing antipsychotic medication for schizophrenia.

BACKGROUND: Numerous economic models have assessed the cost-effectiveness of antipsychotic medications in schizophrenia. It is important to understand what key impacts of antipsychotic medications were considered in the existing models and limitations of existing models in order to inform the development of future models. OBJECTIVES: This systematic review aims to identify which clinical benefits, clinical harms, costs and cost savings of antipsychotic medication have been considered by existing models, to assess quality of existing models and to suggest good practice recommendations for future economic models of antipsychotic medications. METHODS: An electronic search was performed on multiple databases (MEDLINE, EMBASE, PsycInfo, Cochrane database of systematic reviews, The NHS Economic Evaluation Database and Health Technology Assessment database) to identify economic models of schizophrenia published between 2005-2020. Two independent reviewers selected studies for inclusion. Study quality was assessed using the National Institute for Health and Care Excellence (NICE) checklist and the Cooper hierarchy. Key impacts of antipsychotic medications considered by exiting models were descriptively summarised. RESULTS: Sixty models were included. Existing models varied greatly in key impacts of antipsychotic medication included in the model, especially in clinical outcomes used for assessing reduction in psychotic symptoms and types of adverse events considered in the model. Quality of existing models was generally low due to failure to capture the health and cost impact of adverse events of antipsychotic medications and input data not obtained from best available source. Good practices for modelling antipsychotic medications are suggested. DISCUSSIONS: This review highlights inconsistency in key impacts considered by different models, and limitations of the existing models. Recommendations on future research are provided.

Cost variability of antipsychotics according to pharmaceutical establishments in Lima, Peru. / Variabilidad de costos de antipsicóticos según establecimientos farmacéuticos en Lima, Perú.

The objectives of the study were to determine the cost variability of antipsychotics in public (hospi tals) and private pharmaceutical establishments (pharmacies and clinics), calculate the cost variability of antipsychotics between establishments and estimate the cost of monthly maintenance treatment with antipsychotics. A cost analysis study was performed, unit costs of antipsychotics were obtained from the Peruvian Pharmaceutical Products Observatory. The results show that the cost variability of antipsycho tics was greater in pharmacies and clinics than in hospitals, and the analysis of cost variability between pharmaceutical establishments showed that the cost of an antipsychotic in a pharmacy and clinic was 1.3 to 140 times and 2.8 to 124 times, respectively, the cost of the drug in a hospital. The cost of monthly maintenance treatment varied from S/3 to S/2130 according to the drug and pharmaceutical establish ment.

Los objetivos del estudio fueron determinar la variabilidad de costos de antipsicóticos en establecimien tos farmacéuticos públicos (hospitales) y privados (farmacias y clínicas), calcular la variabilidad de cos tos de antipsicóticos entre establecimientos y estimar el costo de tratamiento mensual de mantenimiento con antipsicóticos. Se realizó un estudio de análisis de costos, los costos unitarios de los antipsicóticos se obtuvieron del Observatorio Peruano de Productos Farmacéuticos. Los resultados muestran que la va riabilidad de costos de los antipsicóticos fue mayor en farmacias y clínicas que en hospitales, y el análisis de variabilidad de costos entre establecimientos farmacéuticos mostró que el costo de un antipsicótico en una farmacia y clínica fue 1,3 a 140 veces y de 2,8 a 124 veces, respectivamente, el costo que tuvo el fármaco en un hospital. El costo de tratamiento mensual de mantenimiento varió de S/ 3 a S/ 2130 según el fármaco y establecimiento farmacéutico.

Spillover effects of state medicaid antipsychotic prior authorization policies in US commercially insured youth.

PURPOSE: To evaluate spillover effects of Medicaid antipsychotic prior authorization (PA) policies among commercially insured youth. METHODS: Commercially insured youth residing in nine US states that implemented PA exclusively for antipsychotics in 2011 or 2012 were identified using a 10% random sample of enrollees in the IQVIA PharMetrics Plus database spanning 2007 to 2015. Youth were included if they were ≤18 years, met the age criteria of the PA at the time of dispensing, and had at least 1 month of prescription drug coverage from 2007 to 2015. The primary outcome of interest was the monthly prevalence of antipsychotics. We implemented segmented regression of interrupted time series analysis to estimate changes in the monthly prevalence of targeted medications, overall and stratified by age. Trends were compared in the 4-year period before and the 3-year period after implementation of PA policies. RESULTS: Antipsychotics prescribing significantly decreased 6.74/10 000 (95% CI, -9.04 to -4.44) enrollees per month immediately after PA implementation. However, PA was not associated with significant long-term trend changes (-0.06; 95% CI, -0.16 to 0.03). Antipsychotic prescribing in children <12 years-old significantly decreased 0.14/10 000 (95% CI, -0.21 to -0.07) enrollees per month after PA implementation, while prescribing in adolescents 12 to 18 years-old significantly increased 0.32/10 000 (95% CI, 0.16 to 0.47) enrollees per month. CONCLUSION: While Medicaid PA polices for antipsychotic oversight did not affect overall prescribing, there were spillover effects in U.S. commercially insured children <12 years-old. This suggests that state-level Medicaid policies intended to improve the quality of care and safe use of antipsychotics can have broad reach.

Cost-effectiveness and Price of Aripiprazole for Schizophrenia in the Brazilian Public Health System

BACKGROUND: Schizophrenia is a chronic debilitating condition characterized by disorders in thought, affect and behavior. Considering the low effectiveness of antipsychotic drugs for schizophrenia and the potentially high cost of an inadequate choice, a systematic cost-effectiveness evaluation of the list of subsidized antipsychotic drugs is necessary in order to allow an adequate choice of pharmacotherapy for the patient and the financial reality of the Brazilian public health system (SUS). OBJECTIVE: The aims of this study are to conduct a cost-effectiveness analysis of the subsidized antipsychotic drugs for the first-line treatment of schizophrenia in Brazil and aripiprazole, and to discuss a reasonable incorporation price for aripiprazole. METHODS: A three-year Markov model with quarterly cycles was developed in TreeAge Pro® 2009 to assess the cost-effectiveness of six listed oral antipsychotic drugs for the first-line treatment of schizophrenia in the Brazilian public health system (haloperidol, chlorpromazine, risperidone, quetiapine, ziprasidone, and olanzapine) and oral aripiprazole. Outcomes were measured in quality-adjusted life years (QALYs). Reasonable prices for aripiprazole were calculated based on the placement of the drug in the efficiency frontier and the cost-effectiveness ratio of the most efficient comparator. RESULTS: Olanzapine was considered cost-effective adopting any threshold value. If me-too drugs are required to be least as efficient as the comparators, olanzapine would still be cost-effective under 0.031 USD/mg. Aripiprazole was absolutely dominated by risperidone. The sensitivity analysis showed important uncertainty, which was expected. There is, nevertheless, a prominent separation between ziprasidone, quetiapine and the efficiency frontier. Aripiprazole was not considered cost-effective even when its price was set at zero: CER = USD 4,102 vs. USD 3,945 (haloperidol), USD 3,616 (chlorpromazine), USD 3,646 (risperidone) and USD 3,752 (olanzapine) USD/QALY. CONCLUSION: Olanzapine was considered the most cost-effective drug for the first-line treatment of schizophrenia in Brazil. Aripiprazole was dominated by risperidone and was not considered cost-effective against olanzapine. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This work demonstrated, using a price adjustment process, that there is no viable price that would make aripiprazole cost-effective for incorporation in the Brazilian public health system in the first-line of treatment of schizophrenia. The drug can be useful in specific cases, since individual variability of response to antipsychotic drugs is important.

Evaluation of the Cost-effectiveness of Services for Schizophrenia in the UK Across the Entire Care Pathway in a Single Whole-Disease Model.

Importance: The existing economic models for schizophrenia often have 3 limitations; namely, they do not cover nonpharmacologic interventions, they report inconsistent conclusions for antipsychotics, and they have poor methodologic quality. Objectives: To develop a whole-disease model for schizophrenia and use it to inform resource allocation decisions across the entire care pathway for schizophrenia in the UK. Design, Setting, and Participants: This decision analytical model used a whole-disease model to simulate the entire disease and treatment pathway among a simulated cohort of 200 000 individuals at clinical high risk of psychoses or with a diagnosis of psychosis or schizophrenia being treated in primary, secondary, and tertiary care in the UK. Data were collected March 2016 to December 2018 and analyzed December 2018 to April 2019. Exposures: The whole-disease model used discrete event simulation; its structure and input data were informed by published literature and expert opinion. Analyses were conducted from the perspective of the National Health Service and Personal Social Services over a lifetime horizon. Key interventions assessed included cognitive behavioral therapy, antipsychotic medication, family intervention, inpatient care, and crisis resolution and home treatment team. Main Outcomes and Measures: Life-time costs and quality-adjusted life-years. Results: In the simulated cohort of 200 000 individuals (mean [SD] age, 23.5 [5.1] years; 120 800 [60.4%] men), 66 400 (33.2%) were not at risk of psychosis, 69 800 (34.9%) were at clinical high risk of psychosis, and 63 800 (31.9%) had psychosis. The results of the whole-disease model suggest the following interventions are likely to be cost-effective at a willingness-to-pay threshold of £20 000 ($25 552) per quality-adjusted life-year: practice as usual plus cognitive behavioral therapy for individuals at clinical high risk of psychosis (probability vs practice as usual alone, 0.96); a mix of hospital admission and crisis resolution and home treatment team for individuals with acute psychosis (probability vs hospital admission alone, 0.99); amisulpride (probability vs all other antipsychotics, 0.39), risperidone (probability vs all other antipsychotics, 0.30), or olanzapine (probability vs all other antipsychotics, 0.17) combined with family intervention for individuals with first-episode psychosis (probability vs family intervention or medication alone, 0.58); and clozapine for individuals with treatment-resistant schizophrenia (probability vs other medications, 0.81). Conclusions and Relevance: The results of this study suggest that the current schizophrenia service configuration is not optimal. Cost savings and/or additional quality-adjusted life-years may be gained by replacing current interventions with more cost-effective interventions.

Budget impact analysis of long acting injection for schizophrenia in Japan.

Aims: To estimate the budgetary impact of providing additional reimbursement for long acting injections for schizophrenia patients in psychiatric hospital settings in Japan to improve patient outcomes in schizophrenia.Methods: Budget impact analysis of change in reimbursement policy using a prevalence-based model over a five-year time horizon. The results are reported as net change in expenditure and consequent cost/savings in Japanese yen at the time of analysis.Results: The budget impact analysis shows that an increase in reimbursement for LAIs could lead to cumulative savings of an estimated 36.6 billion JPY over five years. These savings result from a decrease in hospitalization costs and an increased usage of LAI (assumed to be 10%). Based on the sensitivity analysis, the saving estimates are most sensitive to change in market share of generic and branded oral antipsychotics.Limitations: Historical data were used to estimate the future costs of drug and hospitalization; however, it is not the best predictor of future, hence a source of potential bias. A good level of treatment adherence with oral antipsychotics was assumed, which is generally not the case; therefore, we might have overestimated the effectiveness of oral atypical antipsychotics. Additionally, the drug cost due to reimbursement might have also been overestimated because in clinical setting, the increase of LAI use may not have reached 10% of the market share. Lastly, patients' behavior was derived from models, which may have loosely approximated the reality.Conclusions: An additional reimbursement for the use of LAI in schizophrenia patients is likely to be cost neutral/cost saving and should be considered as a policy option to improve patient outcomes and budget sustainability.

Comparative cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.

BACKGROUND: Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China. METHODS: A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results. RESULTS: Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY. CONCLUSIONS: Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients in China.

Randomised controlled trial of a treatment adherence programme for prisoners with mental health problems in Spain.

The prevalence of psychiatric disorders is high among prisoners, who often need psychotropic medication, but compliance with treatment is often poor. This combination leads to poorer prisoner-patient health and increased health costs.The aim of this study was to test the impact of a treatment adherence programme (TAP) on medication adherence and subjective well-being among prisoners with mental health problems. We conducted a randomised controlled trial of a treatment adherence programme compared with treatment as usual (TAU) among 183 prisoners with mental health problems. Those in the TAP group showed greater treatment adherence and reported better subjective well-being with medication than those in the TAU group. We conclude that the treatment adherence of prisoners who require medication for mental health problems may be improved through specific intervention programmes. This could make a positive contribution to individual health and well-being.

A Systematic Review of Economic Models Across the Entire Schizophrenia Pathway.

BACKGROUND: Schizophrenia is associated with a high economic burden. Economic models can help to inform resource allocation decisions to maximise benefits to patients. OBJECTIVES: This systematic review aims to assess the availability, quality and consistency of conclusions of health economic models evaluating the cost effectiveness of interventions for schizophrenia. METHODS: An electronic search was performed on multiple databases (MEDLINE, EMBASE, PsycINFO, Cochrane database of systematic reviews, NHS Economic Evaluation Database and Health Technology Assessment database) to identify economic models of interventions for schizophrenia published between 2005 and 2020. Two independent reviewers selected studies for inclusion. Study quality was assessed using the National Institute for Health and Care Excellence (NICE) checklist and the Cooper hierarchy. Model characteristics and conclusions were descriptively summarised. RESULTS: Seventy-three models met inclusion criteria. Seventy-eight percent of existing models assessed antipsychotics; however, due to inconsistent conclusions reported by different studies, no antipsychotic can be considered clearly cost effective compared with the others. A very limited number of models suggest that the following non-pharmacological interventions might be cost effective: psychosocial interventions, stratified tests, employment intervention and intensive intervention to improve liaison between primary and secondary care. The quality of included models is generally low due to use of a short time horizon, omission of adverse events of interventions, poor data quality and potential conflicts of interest. CONCLUSIONS: This review highlights a lack of models for non-pharmacological interventions, and limitations of the existing models, including low quality and inconsistency in conclusions. Recommendations on future modelling approaches for schizophrenia are provided.

Variabilidad de costos de antipsicóticos según establecimientos farmacéuticos en Lima, Perú / Cost variability of antipsychotics according to pharmaceutical establishments in Lima, Peru

RESUMEN Los objetivos del estudio fueron determinar la variabilidad de costos de antipsicóticos en establecimien tos farmacéuticos públicos (hospitales) y privados (farmacias y clínicas), calcular la variabilidad de cos tos de antipsicóticos entre establecimientos y estimar el costo de tratamiento mensual de mantenimiento con antipsicóticos. Se realizó un estudio de análisis de costos, los costos unitarios de los antipsicóticos se obtuvieron del Observatorio Peruano de Productos Farmacéuticos. Los resultados muestran que la va riabilidad de costos de los antipsicóticos fue mayor en farmacias y clínicas que en hospitales, y el análisis de variabilidad de costos entre establecimientos farmacéuticos mostró que el costo de un antipsicótico en una farmacia y clínica fue 1,3 a 140 veces y de 2,8 a 124 veces, respectivamente, el costo que tuvo el fármaco en un hospital. El costo de tratamiento mensual de mantenimiento varió de S/ 3 a S/ 2130 según el fármaco y establecimiento farmacéutico.

ABSTRACT The objectives of the study were to determine the cost variability of antipsychotics in public (hospi tals) and private pharmaceutical establishments (pharmacies and clinics), calculate the cost variability of antipsychotics between establishments and estimate the cost of monthly maintenance treatment with antipsychotics. A cost analysis study was performed, unit costs of antipsychotics were obtained from the Peruvian Pharmaceutical Products Observatory. The results show that the cost variability of antipsycho tics was greater in pharmacies and clinics than in hospitals, and the analysis of cost variability between pharmaceutical establishments showed that the cost of an antipsychotic in a pharmacy and clinic was 1.3 to 140 times and 2.8 to 124 times, respectively, the cost of the drug in a hospital. The cost of monthly maintenance treatment varied from S/3 to S/2130 according to the drug and pharmaceutical establish ment.